Drug shortages can occur for a variety of reasons.The factors currently affecting drug supply are shortages of raw materials, quality control issues which led to voluntary withdrawal and longer production times for some products and competition among drug manufacturers. The problem is expected to ease somewhat with renewed production in some cases and takeover of supply by another company in others. For more details see the environmental scan on Drug Supply Disruptions recently posted on the CADTH website.

In the meantime, healthcare providers are responsible for ensuring patients continue to receive appropriate drug therapy. A general protocol to follow in handling drug shortages is offered below:

Ensure there is a valid indication for the drug. Review the patient’s drug and medical history. For a checklist of criteria to consider, check the CPhA Drug Shortages Guide pg 4 - 6.

Substitution of a different brand of the same drug (molecule):

Check the Saskatchewan Prescription Drug Plan (SPDP) Formulary for interchangeable brands of the same drug; then check for availability of these brands. (Call wholesalers, manufacturers)

If none are available, is there a non-interchangeable brand of the same drug.in the same dosage form? Obtain authorization for substitution from doctor, start at same dose or a reduced dose and titrate to desired effect (especially important if drug has a narrow therapeutic index) and monitor for beneficial and adverse effects. Follow-up with the patient in 24 – 48 hours, as indicated by kinetic and pharmacologic characteristics of the drug.

If none available, is there a different dosage form of the same drug? Obtain authorization for substitution from doctor, start at appropriate dose and titrate to desired effect (especially if narrow therapeutic index) and monitor for beneficial and adverse effects. Follow-up with the patient in 24 – 48 hours as indicated by kinetic and pharmacologic characteristics of the drug.

If no Formulary drug is available, check Drug Product Database for other dosage forms that may be available and proceed as above.

As necessary, consult SPDP regarding coverage for substituted brand.

If no other forms of the same molecule are available, substitution of another drug in the same therapeutic class can be considered. Check the references below for dose equivalence data. This information is not always available. Even when a therapeutically equivalent dose is administered, patients may react differently. Pharmacists should follow-up with the patient frequently until the patient is stabilized on the new medication.

Compounding capsules or tablets in the desired doses when other strengths of drug are available or from bulk powders may be another option, especially in instances where there is not a readily available or acceptable substitute.

In order to provide greater information to health care practitioners and the general public, Canada’s Research Based Pharmaceutical Companies (Rx&D) and the Canadian Generic Pharmaceutical Association (CGPA) began collecting information on behalf of their individual member companies on current and impending drug shortages in the fall of 2011. Rx&D has now turned over its database architecture (i.e. the former Rx&D Drug Shortages Database) and opened its use to non-Rx&D members (i.e. all market authorization holders) who are authorized to sell medicines in Canada, and who may need to use the site to report a drug shortage. Iinformation is being provided on a voluntary basis. It does not necessarily include all pharmaceutical companies in Canada, and therefore there may be gaps in the data. The new database is called the Canadian Drug Shortages Database:

medSask is not responsible for the content of this database, and does not assume any liability that may arise from any use of or reliance on the information contained therein. The information in the database been provided by drug manufacturers, and is presented here for reference purposes only. There is no warranty, representation or guarantee with respect to the accuracy, timeliness or completeness of this information. medSask accepts no responsibility for any errors or omissions, and expressly disclaims any such responsibility.

medSask cannot accept phone, email, fax, or other inquiries about the content of this information. Inquiries regarding specific drug shortages should be directed to the appropriate drug manufacturer as identified. Questions about alternatives for shorted drugs and drug plan coverage for alternatives may be directed to the appropriate provincial drug information service.

The following tables provide suggestions for handling shortages of specific drugs. This information is intended for use by healthcare providers for general informational purposes only. It remains the responsibility of the healthcare provider to use professional judgment in evaluating this information in light of any relevant clinical or situational data. This information is provided without warranty of any kind and medSask and the University of Saskatchewan assume no responsibility and/or legal liability whatsoever for any errors, omissions or inaccuracies contained therein.

PARENTERAL DRUGS

To check current availability status of parenteral drugs go to the Sandoz website and click on Product Supply Information for Healthcare Professionals.

Currently available.Sandoz is the only manufacturer of bretylium.Indicated as last resort for life-threatening ventricular arrhythmia not responding to adequate doses of first-line antiarrhythmic agents. Ventricular Fibrillation - continue with lidocaine, epinephrine, defibrillation, magnesium, procainamideVentricular Tachycardia - procainamide is an alternative

Calcitonin, Salmon, Synthetic

Calcimar 200U/ml (2ml) INJECTION available.All nasal spray calcitonin products have been withdrawn and discontinued from the market due to a small increased rate of cancer (up to2.4 %). DINs became inactive October 1st, 2013 at which time prescribing and dispensing should have ceased. Calcitonin is no longer indicated for osteoporosis. For alternative treatment see ACFP Tools for Practice at http://www.acfp.ca/Portals/0/docs/TFP/20130923_085017.pdf.Calcitonin (salmon synthetic) injectable remains on the market but is indicated only for Paget’s Disease and hypercalcemia. Due to the increased cancer risk the duration of treatment should be limited to the shortest period of time possible and the minimum effective dose.

AvailableSee PDF for therapeutic alternatives. *Note that some of these agents are also in short supply or backordered e.g. phentolamine, esmolol*

Epinephrine / Epipen

Epipen 0.3 mg (adult) indeterminate availability.Epipen Jr (0.15 mg) currently available.Auvi-Q is an autoinjector being imported from the US as per an Interim Order. See details from SCPP. Auvi-Q 0.15 mg - not yet listed at McKessonAuvi-Q 0.3 mg - currently available

Mitomycin for injection 20mg available.Hospitals seeking Mitomycin Injection 20mg on behalf of a patient should contact Health Canada’s Special Access Programme (SAP), who will work with Teva to identify any available product globally and determine if it is suitable to bring into the Canadian market.See PDF for shortage management strategies.

Naloxone Kits are available to Saskatchewan residents without a prescription. Residents may access free health region funded naloxone kits at the following locations. Kits may also be purchased from the following pharmacies.

Anticipated shortage - Pip/Tazo manufacturers (e.g. SDZ, Sterimax, Teligent) may have supply issues as one API manufacturing plant is not in production (explosion at the plant) which means that all API has to come from the sole remaining API manufacturer which is challenged in covering the global market.

AvailableReserve current stock for patients with cancer protocols which require periodic injections of vitamin B!2 to prevent toxicity Restrict parenteral use to patients with severe neurologic involvement or with vomiting, diarrhea or bowel resection, or chidlren with severe deficiency when rapid restoration of stores is desiredAlternatives: Oral or sublingual route:Adult - 1,000 to 2,000 mcg/day inititally to treat deficiency, followed by maintenance dose of 1000 mcg/day Children - Not well defined. Doses of up to 1000 mcg/day orally are used for pernicious anemia.

Rasilez and Rasilez HCT are no longer available through McKesson.There are no generics and no other Renin Inhibitors available.Now distributed by Innomar Strategies; 1-888-996-9049 ordered directly or through Kohl & Frisch wholesale.There is a $250 ordering minimum or a $20 fee if below minimum.

Allopurinol (Zyloprim)

All strengths and brands available from various manufacturers.Zyloprim - all strengths available.Discontinuation in patients with mild gout and no attacks for years may be considered.Alternatives:Xanthine oxidase inhibior: febuxostat (Uloric) 80 mg PO once daily. (new, $$)2nd line prophylaxis:Colchicine 0.6 - 1 mg PO once daily; reduce dose in elderly, renal impairmentUricosuric agents: ineffective if CrCl <50 ml/min; not in urate over-producers; not if history of nephrolithiasis; liberal fluid intake required:- Probenecid: inital dose 250 mg PO BID, titrate to 0.5 - 2 g / day in two to three divided doses- Sulfinpyrazone: inital 100-200 mg PO BID, increase dose to 200 - 400 mg PO BID

No manufacturers are currently marketing oral ampicillin suspension.Ampicilllin 250 and 500mg capsules available.Alternatives Compound suspension from oral ampicillin capsules (See detail document) Substitue a different antibiotic which is active against the organism causing the infection

Dostinex: AvailableApotex brand available November 8, 2018 - now listed as a benefit on SK FormularySee PDF for details.

Calcitonin nasal spray

All nasal spray calcitonin products have been withdrawn from the market and discontinured due to a small increased rate of cancer (up to2.4 %). DINs became inactive October 1st, 2013 at which time prescribing and dispensing should have ceased. Calcitonin is no longer indicated for osteoporosis. For alternative treatment see ACFP Tools for Practice at http://www.acfp.ca/Portals/0/docs/TFP/20130923_085017.pdf.

Calcitonin (salmon synthetic) injectable remains on the market but is indicated only for Paget’s Disease and hypercalcemia. Due to the increased cancer risk the duration of treatment should be limited to the shortest period of time possible and the minimum effective dose.

Dalacin C granules for solution 75mg/5ml available.Options: capsules (150, 300 mg) can be opened up and mixed with water of food (not an approved method of administration) - see PDF for more details; parenteral injection for severe infectionTherapeutic alternatives - See PDF

Frisium - available. Lundbeck the manufacturer of Frisium has discontinued production of the name brand Frisium. Current inventory is expected to be depleted by August 2018. For more information Lundbeck’s Medical Information at 866‑880‑4636 will address questions or concerns.Alternatives: clonazepam (or other benzodiazepine); anticonvulsant appropriate for seizure disorder

Clobazam must be tapered before stopping if not switching to another BZD - see PDF.

Capsules currently available in both strengths. TEVA 125mg/5ml (100ml size) suspension available.Alternatives:Cephalexin is an appropriate alternative for an infection in which cloxacillin is indicated: abscess (breast)/mastitis (mild); carbuncles (mod-severe); bursitis, septic; cellulitis (extremities and facial); dacrocystitis in adult; impetigo (mod-severe); osteomyelitis (step down in children)

Co-trimoxazole (sulfamethoxazole/trimethoprim)

Both DS and regular strength tablets available from either Teva or ApotexSuspensions TEVA - MANUFACTURER CANNOT SUPPLY FOR INFORMATION CALL 800-268-4127 INDETERMINATE AVAILABILITY DATEOptions: Use other methods of administration.Alternatives: A different antibiotic with a similar spectrum of activity

AvailableIn the event of a shortage:Alternative: Substitute same strength valproic acid formulation. May be increased GI adverse effects - take with food. Monitor for continued control of seizures / mood.

Alternatives: other macrolides are available as liquid formulations ie. Azithromycin, Clarithromycin. Compounding not recommended as cost-prohibitive, lack of formulas readily accessible and other options readily available.

Fenofibrate

Fenofibrate Micronized Capsule 200mg (Apotex) currently available.The following fenofibrate formulations are considered to have equivalent bioavailability:

In the likely event both fleicanide and propafenone are short, no blanket recommendation can be made. Ideally consult cardiology; if unavailable, please phone medSask for individual assessment and include as much patient history as possible including - but not limited to: the type of arrhythmia being treated; current medications, past medications for the arrythmia and reason for discontinuation, if known; other medical conditions; allergies.

Bulk powder is not listed in the catalogues for either Medisca or Xenex.

In general, when switching from IR lithium to SR, the total daily dose of lithium is the same. Lithmax given either BID or at HS can be used.The CPhA Product Monograph states that: Once patients are stabilized on a maintenance dose, the dosage schedule may be changed to a once-daily regimen.The Product Monograph for LITHMAX ( https://www.aapharma.ca/downloads/en/PIL/2016/Lithmax-PM.pdf) states that: Lithium carbonate sustained-release tablets should be swallowed whole or broken in half. They should not be chewed or crushed. N.B.: Blood samples for serum lithium determination should be drawn prior to the next dose and when lithium concentrations are relatively stable (i.e. 10 to 14 hours after the previous dose of lithium). Total reliance must not be placed on serum levels alone. Accurate patient evaluation requires both clinical assessment and laboratory analyses.Promotion Express Express Express Express Promotion Express Promotion Promotion Express Promotion Promotion Promotion Express Express Promotion

Adalat XL 20 mg tablets not available until 07 Oct 2018; no other manufacturers make 20 mg tablets.Currently 30 mg and 60 mg tablets still available.See document for information regarding switching to a different calcium channel blocker.

*Iodoquinol (Diodoquin) is made by Glenwood as 210 mg and 650 mg tablets. As of Feb.17, 2014, only the 210 mg tablets are available. Diodoquin is not available through McKesson but is distributed through Kohl & Frisch, AmerisourceBergen, Procurity, uniPHARM.

Penicillin V

300mg tablets currently available.

Suspension 125mg/5ml and 300mg/5ml not currently available - resupply - no date for availability according to McKesson catalogue

Alternative long acting tablets providing 8 mEq K+:Euro-K600 (NPN 02246734) 600 mg long acting tabletApo-K (NPN 00602884) 600 mg long acting tabletJamp K-8 (NPN 80013005) 600 mg long acting tabletNote: These products contain the same strength of KCl in a similar dosage form to Slow-K and are the closest alternatives. However, the products are not interchangeable. If patient is near the high or low ends of the potassium reference range or if patient has a history of frequent fluctuations, closer monitoring after transition is prudent. Note: Inventory of the above products seems to fluctuate frequently.

Alternative solid dosage forms providing 8 mEq K+:Micro-K Extencaps (NPN 02042304)Promotion Express Express Promotion Promotion Promotion Promotion Promotion Express Express Express Express Express Promotion Promotion Express Note: Micro-K contains the same strength of KCl in a different, yet still modified release, dosage form. If patient is near the high or low ends of the potassium reference range or if patient has a history of frequent fluctuations, closer monitoring after transition is prudent.

KCl Oral Solution providing 1.33 mEq/ml: PMS-Potassium Chloride (NPN 02238604 )Note: Because the absorption pattern will be quite different between Slow-K and the liquid, closer monitoring of all patients after transition is prudent.

Apotex 150mg and 300mg available September 28, 2018.SANIS 150mg available October 12, 2018; 300mg available November 8, 2018.Mylan 150mg and 300 mg available October 12, 2018.Rythmol (BGP) 150mg and 300mg available October 12, 2018.

In the likely event both fleicanide and propafenone are short, no blanket recommendation can be made. Ideally consult cardiology; if unavailable, please phone medSask for individual assessment and include as much patient history as possible including, but not limited to: the type of arrhythmia being treated; current medications, past medications for the arrythmia and reason for discontinuation, if known; other medical conditions; allergies.

Pyrantel pamoate suspension

Jamp Pharma Pyrantel Pamoate suspension 50mg/ml and 125mg tablets are available.Combantrin suspension has been discontinued.Combantrin 125 mg tablets available.For patients unable to take tablets, the tablet can be crushed and mixed with a soft food immediately before administering.

Generics availableIf dose corresponds to tablet strength (75, 150, 300 mg), tablet can be crushed and mixed with soft food such as applesauce immediately before administering.Extemporaneous compounding: See PDF for details

Various brands of valsartan have been Sweater style Boutique SONOMA Pullover life wx1wY8qp by Health Canada.Supply of valsartan only tablets seems limited, if available at all. Check with your wholesaler. Currently several brands of valsartan/HCTZ are available.Express Express Promotion Promotion Promotion Promotion Express Express Promotion Promotion Promotion Express Express Express Express Promotion See document for information about switching to a different ARB.